DNA vaccine offers hope against tuberculosis

A new DNA vaccine may offer hope in the fight against one of the world's biggest killers - tuberculosis.

Some two million people die of TB every year. And one third of the world's population, about two billion people, carry TB without developing symptoms. Furthermore, many of the people who fall ill and recover can then relapse in the future.

Now, a South Korean team led by Youngchul Sung at Pohang University of Science and Technology in Pohang has developed a vaccine which, when given with therapeutic drugs to sick mice, significantly reduced rates of relapse or reinfection.

"It's an important advance because reinfection is significant in areas of the world where there is a lot of TB," says Douglas Lowrie at the National Institute for Medical Research in London, UK, whose group researches TB vaccines. "It is also significant because it shows what is possible - you can use a DNA vaccine in infections and generate a level of immunity you would like to see in a preventive vaccine. It's possible, at least in mice."

A preventive DNA vaccine would be extremely useful as the efficacy of the traditional BCG vaccine against TB varies widely throughout the world. While it is about 85% effective in the UK, for example, it has no efficacy in some other countries. This lack of efficacy is thought to result from environmental exposure to microbes from the Mycobacterium genus, to which M. tuberculosis belongs.

Weakened or dead

DNA vaccines invoke immunity against an infectious agent by presenting particular genes from an organism to the immune system. The proteins the genes code for appear on the surface of the bacterium and are recognised as foreign. So DNA vaccines can stimulate a response without the need for injecting a weakened or dead form of a bug.

Sung's vaccine is not the first DNA vaccine against TB to show a beneficial effect in mice, says Lowrie, who developed the first DNA vaccine for TB in 1994. But it is "possibly one of the most effective to be reported". And when given with chemotherapy, the DNA vaccine also speeded up the recovery of the mice.

This could be very significant if it worked in humans, as TB drugs must be taken for six to nine months to rid a person of the disease. Often this long course proves too difficult, especially in developing countries where expense and availability can be an issue. Not finishing a course of drugs can mean a person is not completely cured and can either relapse or be reinfected in the future. And it can lead to multi-drug-resistant strains.

Sung's group used two genes from the TB bacterium and spliced them into the DNA vaccine. This vaccine was injected into mice which had already been exposed to and contracted TB. It was given alongside standard drug treatment.

The researchers found that this combination completely blocked the reactivation of TB many weeks later. By contrast, in the control group of mice, the bug was reactivated in response to a chemical stimulus in 60% of the animals.

The vaccine, combined with drug therapy, also significantly prevented reinfection when the mice were exposed to another strain 66 weeks after their first infection.

Journal reference: Gene Therapy (DOI: 10.1038/sj.gt.3302465)

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